Cancer-related fatigue (CRF) is one of the most common side effects during or after cancer treatment. Cancer-related fatigue (CRF) is defined, by the National Comprehensive Cancer Network (NCCN), as “a persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning and deteriorates the quality of patient's life”. Cancer-related fatigue (CRF) may be differentiated from general fatigue in that it is not relieved by rest and is not primarily caused by physical activity.
Cancer patients describe cancer-related fatigue (CRF) as feeling very severe, chronic, and distressing, and not being relieved by rest. Many studies report that, among the cancer-related side effects, CRF has the most negative impact on the quality of the lives of cancer patient and restricts their normal lives.
It is reported that almost all cancer patients experience the incidence of cancer-related fatigue (CRF) during the cancer treatment, depending on the applied treatment method and period. That is, it is reported that the cancer-related fatigue (CRF) incidence of patients not receiving anticancer treatments is about 75% and the CRF incidence of patients receiving chemotherapy or radiation therapy is higher. With respect to the extent of cancer-related fatigue (CRF), patients having undergone bone marrow transplants and chemotherapy generally shows more severe cancer-related fatigue (CRF) than patients having undergone adjuvant chemotherapy without bone marrow transplants, and patients having undergone adjuvant chemotherapy complain of cancer-related fatigue (CRF) more frequently than patients having undergone radiation therapy (Ikjung, 2010).
Several side effects or general symptoms (e.g., depression, anxiety, pain, nausea, vomiting, insomnia, and anemia), resulting from cancer and cancer treatment, including cancer-related fatigue (CRF), require excessive rest and cause muscular weakness, muscular atrophy, muscular function impairment, and cardiovascular function impairment. Patient's inactivity due to bed rest or the like aggravates the patient's daily living activity.
Most medicine therapies for cancer-related fatigue (CRF) have the intention of treating an allopathic effect rather than approach through cause, and cannot solve problems generated during cancer treatment, such as deterioration in physical strength, loss of muscle mass, and decline in muscle function.
A primary pharmaceutical activity of modafinil, which is a drug associated with cancer-related fatigue (CRF), promotes awareness. Modafinil promotes awareness in models simulating clinical situations, such as obstructive sleep apnea syndrome (English bulldog, sleep-disordered breathing model, Panckeri et al., 1996) and paroxysmal sleep (paroxysmal sleep dug, Shelton et al., 1995) as well as rat (Touret et al., 1995; Edgar and Seidel, 1997), cat, dog (Shelton et al., 1995), and non-human primate (Hernant et al., 1991). In addition, modafinil is a drug that is active in the central nervous system, and is described as a medicine that is useful in the treatment of Parkinson's disease (U.S. Pat. No. 5,180,745), in the protection of cerebral tissue from ischemia (U.S. Pat. No. 5,391,576), in the treatment of urine and urinary incontinence (U.S. Pat. No. 5,401,776), and in the treatment of obstructive sleep apnea syndrome and central origin diseases (U.S. Pat. No. 5,612,379).
Currently, modafinil is in the process of being tested in clinical trials as a cancer-related fatigue (CRF) therapeutic agent by co-administration with docetaxel-based chemotherapy to metastatic breast cancer patients and prostate cancer patients complaining of cancer-related fatigue (CRF), and also by the combined treatment with radiation therapy to solid cancer patients complaining of cancer-related fatigue (CRF) (J. Clin. Oncol. 30, 2012).
The main components of ginseng are ginseng saponines called “ginsenosides”, which is designated by specifically differentiating only ginseng saponines from several saponines of plants. Saponines among the ginseng components have pharmaceutical efficacies, such as depressing central nervous system, mental stability, killing pains, improving memory, protecting liver injury, promoting protein and lipid synthesis, anti-diabetic activity, anti-stress activity, promoting the production of antioxidant active substances, immune regulation, inhibiting platelet aggregation, and anti-aging activity, as well as anti-cancer, anti-allergy, and anti-inflammatory activities.
Meanwhile, there are known saponines, such as ginsenosides Rb1, Rb2, and Rc, which are the main components exhibiting pharmaceutical efficacies of ginseng. However, it has been known that compound K and ginsenosides Rh1, Rh2, and Rg3, which are contained in ginseng in trace amounts, are the components which substantially have anticancer and anti-allergic activities and inhibit cancer cell metastasis.
With respect to ginsenosides that are known to have an effect on cancer-related fatigue (CRF), ginsenoside Rh2 has been known as a composition for preventing or treating cancer-related fatigue (CRF) (Chinese Patent No. 101612159, 31 Aug. 2011), and it has been reported that Rg3 is not dose-dependent on the fatigue relieving effect in patients having undergone cancer cell removal (Kou Xiao-ge et al., National Medical Frontiers of China, 2010, Abstract), but showed an anti-fatigue effect when ginsenoside Rg3 was intranasally administered (Wenyan et al. 2008). However, there has been no patent or research document with respect to a synergetic cancer-related fatigue (CRF) relieving effect depending on the combination of ginsenosides Rh2 and/or Rg3 or the contents thereof.
Unlike general fatigue that is overcome by rest, most medicine therapies for cancer-related fatigue (CRF) have an intention of treating an allopathic effect rather than approach through cause, and cannot solve problems that are generated during cancer treatment, such as deterioration in physical strength, loss of muscle mass, and decline of muscle function. It is recently reported that the dominant mechanisms with respect to the cause of cancer-related fatigue (CRF) in cancer patients having undergone chemotherapy or radiation therapy are increased activities of pro-inflammatory cytokines and deteriorated glycogen synthesis in muscles.
Therefore, the present inventors found that a composition containing a processed ginseng powder or processed ginseng extract, of which trace amounts of ginsenoside components, Rh2 and Rg3, are increased by preparing a saponin-decomposing enzyme and then using hydrolysis through the saponin-decomposing enzyme and an organic acid, is very effective in the prevention and treatment of cancer-related fatigue (CRF), and then the present inventors completed the present invention.